Multiple kinases regulate mafA expression in the pancreatic beta cell line MIN6.
MafA is a basic leucine zipper transcription factor expressed within the beta cells of the pancreas and is required to maintain normal glucose homeostasis as it is involved in various aspects of beta cell biology. MafA protein levels are known to increase in response to high glucose through mechanisms that have yet to be fully characterized. We investigated whether discrete intracellular signaling events control mafA expression. We found that the general kinase inhibitor staurosporine induces mafA expression without altering the stability of the protein. Inhibition of the MAP-kinase JNK mimics the effects of staurosporine on the expression of mafA. Calmodulin kinase and calcium signaling are also important in stimulating mafA expression by high glucose. However, staurosporine, JNK, and calmodulin kinase have different effects on the induction of insulin expression. These data reveal that MafA levels are tightly controlled by the coordinated action of multiple kinase pathways.
Vanderford
Nathan L
NL
Department of Molecular and Cellular Biochemistry, University of Kentucky, College of Medicine, 741 South Limestone Street, Lexington, KY 40536, USA.
Cantrell
Jamie E L
JE
Popa
Gabriel J
GJ
Ozcan
Sabire
S
D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003920:Diabetes Mellitus / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051473:Maf Transcription Factors, Large / Q000096:biosynthesis* / Q000502:physiology*; D008954:Models, Biological; D015398:Signal Transduction; D019311:Staurosporine / Q000494:pharmacology; D014158:Transcription, Genetic
D007328:Insulin; C485159:MAFA protein, human; D051473:Maf Transcription Factors, Large; D048670:MAP Kinase Kinase 4; D019311:Staurosporine; D005947:Glucose; D002118:Calcium